| Antitumor activity of Noscapine in combination with Doxorubicin in triple negative breast cancer. | |
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MedLine Citation:
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PMID: 21423660 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: The aim of this study was to investigate the anticancer activity and mechanism of action of Noscapine alone and in combination with Doxorubicin against triple negative breast cancer (TNBC). METHODS: TNBC cells were pretreated with Noscapine or Doxorubicin or combination and combination index values were calculated using isobolographic method. Apoptosis was assessed by TUNEL staining. Female athymic Nu/nu mice were xenografted with MDA-MB-231 cells and the efficacy of Noscapine, Doxorubicin and combination was determined. Protein expression, immunohistochemical staining were evaluated in harvested tumor tissues. RESULTS: Noscapine inhibited growth of MDA-MB-231 and MDA-MB-468 cells with the IC(50) values of 36.16±3.76 and 42.7±4.3 µM respectively. The CI values (<0.59) were suggestive of strong synergistic interaction between Noscapine and Doxorubicin and combination treatment showed significant increase in apoptotic cells. Noscapine showed dose dependent reduction in the tumor volumes at a dose of 150-550 mg/kg/day compared to controls. Noscapine (300 mg/kg), Doxorubicin (1.5 mg/kg) and combination treatment reduced tumor volume by 39.4±5.8, 34.2±5.7 and 82.9±4.5 percent respectively and showed decreased expression of NF-KB pathway proteins, VEGF, cell survival, and increased expression of apoptotic and growth inhibitory proteins compared to single-agent treatment and control groups. CONCLUSIONS: Noscapine potentiated the anticancer activity of Doxorubicin in a synergistic manner against TNBC tumors via inactivation of NF-KB and anti-angiogenic pathways while stimulating apoptosis. These findings suggest potential benefit for use of oral Noscapine and Doxorubicin combination therapy for treatment of more aggressive TNBC. |
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Authors:
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Mahavir B Chougule; Apurva R Patel; Tanise Jackson; Mandip Singh |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-03-15 |
Journal Detail:
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Title: PloS one Volume: 6 ISSN: 1932-6203 ISO Abbreviation: PLoS ONE Publication Date: 2011 |
Date Detail:
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Created Date: 2011-03-22 Completed Date: 2011-07-05 Revised Date: 2011-11-25 |
Medline Journal Info:
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Nlm Unique ID: 101285081 Medline TA: PLoS One Country: United States |
Other Details:
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Languages: eng Pagination: e17733 Citation Subset: IM |
Affiliation:
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College of Pharmacy, University of Hawaii, Hilo, Hawaii, United States of America. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiogenesis Inducing Agents
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metabolism Animals Antineoplastic Agents / pharmacology, therapeutic use* Antineoplastic Combined Chemotherapy Protocols / pharmacology, therapeutic use* Apoptosis / drug effects Apoptosis Regulatory Proteins / metabolism Breast Neoplasms / blood supply, drug therapy*, enzymology, pathology Caspase 3 / metabolism Cell Line, Tumor Cell Proliferation / drug effects Cell Survival / drug effects DNA Fragmentation / drug effects Doxorubicin / pharmacology, therapeutic use* Drug Synergism Female Humans Immunohistochemistry Mice NF-kappa B / metabolism Neovascularization, Pathologic / drug therapy, pathology Noscapine / pharmacology, therapeutic use* Xenograft Model Antitumor Assays |
| Grant Support | |
ID/Acronym/Agency:
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5S06GM008111-36/GM/NIGMS NIH HHS; G12 RR003020-26/RR/NCRR NIH HHS; G12 RR003020-27/RR/NCRR NIH HHS; G12RR03020-11/RR/NCRR NIH HHS; S06 GM008111-36/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Angiogenesis Inducing Agents; 0/Antineoplastic Agents; 0/Apoptosis Regulatory Proteins; 0/NF-kappa B; 128-62-1/Noscapine; 23214-92-8/Doxorubicin; EC 3.4.22.-/Caspase 3 |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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